02204nas a2200529   4500000000100000008004100001653001200042653003400054653001500088653001000103100001000113700001400123700000900137700000900146700000900155700001000164700001100174700001100185700001200196700001000208700000900218700001200227700001100239700001000250700000900260700001000269700001200279700001000291700001000301700001700311700001100328700001000339700001000349700000900359700001200368700001100380700001100391700001600402700001100418700001200429700001000441700001200451245009300463050001300556520109100569022001401660       2015                            d10aleprosy10aGenome-Wide Association Study10aEvaluation10aChina1 aLiu H1 aIrwanto A1 aFu X1 aYu G1 aYu Y1 aSun Y1 aWang C1 aWang Z1 aOkada Y1 aLow H1 aLi Y1 aLiany H1 aChen M1 aBao F1 aLi J1 aYou J1 aZhang Q1 aLiu J1 aChu T1 aAndiappan AK1 aWang N1 aNiu G1 aLiu D1 aYu X1 aZhang L1 aTian H1 aZhou G1 aRotzschke O1 aChen S1 aZhang X1 aLiu J1 aZhang F00aDiscovery of six new susceptibility loci and analysis of pleiotropic effects in leprosy.  aLIU 20153 a<p>Genome-wide association studies (GWAS) have led to the discovery of several susceptibility loci for leprosy with robust evidence, providing biological insight into the role of host genetic factors in mycobacterial infection. However, the identified loci only partially explain disease heritability, and additional genetic risk factors remain to be discovered. We performed a 3-stage GWAS of leprosy in the Chinese population using 8,313 cases and 16,017 controls. Besides confirming all previously published loci, we discovered six new susceptibility loci, and further gene prioritization analysis of these loci implicated BATF3, CCDC88B and CIITA-SOCS1 as new susceptibility genes for leprosy. A systematic evaluation of pleiotropic effects demonstrated a high tendency for leprosy susceptibility loci to show association with autoimmunity and inflammatory diseases. Further analysis suggests that molecular sensing of infection might have a similar pathogenic role across these diseases, whereas immune responses have discordant roles in infectious and inflammatory diseases.</p>
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